Immune System Disease, Psoriasis (PsO), Skin Disease, Skin Diseases, Papulosquamous
Conditions
Keywords
Phase 1, Healthy Participants, HL40626S, Oral Tablets, SAD, MAD, Safety, Pharmacokinetics, Immunogenicity, Pharmacodynamics
Brief summary
This is a single-centre, randomized, double-blind, placebo-controlled Phase 1 study to assess safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of HL40626S tablets following single and multiple ascending oral doses to healthy adult participants aged 18-55 years.
Detailed description
In Part 1 (Single Ascending Dose, SAD), healthy participants are randomized to receive a single fasting oral dose of HL40626S tablets or matching placebo across five sequential ascending dose cohorts. Each cohort enrolls 8 participants. Sentinel dosing is implemented for every cohort to monitor initial safety before full cohort enrolment. In Part 2 (Multiple Ascending Dose, MAD), healthy participants are randomized to receive once-daily fasting oral doses of HL40626S tablets or matching placebo for 14 consecutive days across three sequential ascending dose cohorts. Each cohort enrolls 8 participants. All decisions to escalate to the next dose cohort were reviewed and approved by an independent Safety Review Committee (SRC) following complete data review of the preceding cohort.
Interventions
DRUGHL40626S tablets
Oral study tablets administered in a dose-escalation design
DRUGHL40626S placebo
Inactive oral placebo tablets matching the active drug dose-escalation scheme
Sponsors
HighsLab Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The study will be double-blinded. The participants and the clinical personnel involved in the collection, monitoring, revision, or evaluation of AEs, or personnel who could have an impact on the outcome of the study will be blinded with respect to the participant's treatment assignment (HL40626S or placebo).
Intervention model description
Sequential dose-escalation design with separate single ascending dose (SAD) and multiple ascending dose (MAD) cohorts, randomized double-blind placebo control.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Capable of understanding the written informed consent document; willingly provides valid, signed written informed consent; willing and able to comply with the schedule, requirements and restrictions of the study. 2. Between the ages of 18.0 and 55.0 years (inclusive) at the time of Screening. 3. BMI between 18.0 and 32.0 kg/m2 (inclusive) at the time of Screening, with a body weight ≥ 50 kg. 4. In good general health, as determined by the Investigator. 5. Female participants must be non-pregnant and non-lactating. 6. Female participants must be of non-childbearing potential, or agree to use dual contraception methods (female participants exclusively in same-sex relationships are exempt from the above contraception requirements), and abstain from ova (egg) donation throughout the entire duration of the study and for at least 90 days after the last dose, and have negative pregnancy test results at Screening (serum) and Day -1 (urine). (Note: As this is a first-in-human \[FIH\] study, the applicable t₁/₂ and corresponding restriction period may be adjusted based on emerging PK data). 7. Male participants with female partners of reproductive potential must agree to practice complete abstinence or to use a condom (male participant) plus an additional highly effective method (female partner) of contraception for the duration of the study and for at least 90 days after last dosing (Male participants exclusively in same-sex relationships are exempt from the above contraception requirements); all male participants must also agree to refrain from sperm donation for at least 90 days after the last dose. (Note: As this is a FIH study, the applicable t₁/₂ and corresponding restriction period will be adjusted based on real-time PK data).
Exclusion criteria
1. Clinically significant abnormal medical history, such as gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, drug hypersensitivity, as determined by the Investigator, any abnormal findings on physical examination, VS measurements, ECG or laboratory tests at Screening, Admission or pre dose on Day 1 that, in the opinion of the Investigator, could jeopardize achieving the study objectives and/or compromise the participant's safety. 2. Any of the following ECG findings at Screening, Admission and/or pre dose on Day 1: 1. Any out-of-range ECG parameter(s) or abnormal finding(s) considered clinically significant by the Investigator. 2. Any ECG finding that, in the opinion of the Investigator, may compromise interpretation of ECG for cardiac safety assessments and/or complicate interpretation of events that may occur post dose (e.g., QT not accurately measurable, conduction abnormalities). 3. Participants with QTcF \>450 msec (if male) or \>470 msec (if female) will be excluded. 3. Resting HR \< 40 bpm or \>100 bpm when vital signs are measured at Screening 4. SARS-CoV-2 positive by PCR at Admission regardless of symptoms. 5. Unstable cardiovascular disease, including recent (within 6 months of screening) myocardial infarction or cardiac arrhythmia. 6. Ongoing liver disease or unexplained liver function test (LFT) elevations, defined as ALT, AST, gamma glutamyltransferase (GGT), alkaline phosphatase (ALP) or total/direct bilirubin \> upper limit of the reference range (ULRR) at Screening or Admission. Participants with confirmed Gilbert's syndrome will not be permitted to enroll in the study. 7. Indications of pre-metabolic syndrome and/or systemic inflammation, as suggested by high-sensitivity C-reactive protein (hsCRP) of \> 3 mg/L, elevated erythrocyte sedimentation rate (Male ≥ 15 mm/hr, Female ≥ 20 mm/hr) or Hemoglobin A1c (HbA1c) \>5.3% at Screening. 8. History of cancer (malignancy) with the exception of basal or squamous cell carcinoma of the skin. 9. Respiratory tract infection (upper and/or lower) treated with antibiotics within 12 weeks of Screening. 10. Clinically significant infection or known inflammatory condition or history of clinically significant infection within 28 days prior to study drug administration on Day 1 that, in the opinion of the Investigator, would affect the participant's ability to participate in the trial. 11. History of drug or alcohol abuse (as defined by DSM-V) within 12 months prior to Screening. 12. Positive test result for alcohol (breath) or drugs of abuse (urine) at Screening or Admission. 13. Positive serology result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab) or human immunodeficiency virus antibody (HIV Ab) at Screening. 14. Active or recent herpes simplex or herpes zoster infection, if considered clinically relevant as per investigator discretion. 15. Venous access considered inadequate for PK sample collection; history of evidence of adverse symptoms associated with phlebotomy or blood donation. 16. Participation in a study of any investigational drug, device, biologic or other agent within 30 days (or 5 half-lives, whichever is longer \[as applicable\]) prior to Day 1. 17. Loss or donation of blood \>500 mL (within 30 days prior to Screening); donation of bone marrow or peripheral stem cells (within 90 days prior to Day 1); or donation of plasma (within 7 days prior to Screening). 18. No more than 10 standard drinks per week per NHMRC alcohol guidelines within 90 days prior to screening. 19. Use of alcohol within 72 hours prior to study drug administration on Day 1. 20. Use of prescription drugs within 14 days (or 5 half-lives, whichever is longer), or non-prescription drugs and/or herbal supplements within 7 days (or 5 half-lives, whichever is longer) prior to study drug administration on Day 1. Exception: hormonal contraceptives, acetaminophen ≤ 1 gram/day or ibuprofen ≤ 800 mg/day may be administered at Investigator's discretion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Parts 1 (SAD) and 2 (MAD): Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | From signed informed consent through Day 15 for SAD and Day 29 for MAD. | Assess incidence, severity, causality and clinical outcome of treatment-emergent adverse events (TEAEs) graded per CTCAE Version 6.0 to characterize the safety and tolerability of HL40626S in Part 1 (SAD) and Part 2 (MAD). |
| Parts 1 (SAD) and 2 (MAD): Incidence of serious adverse events (SAEs) [Safety and Tolerability] | From signed informed consent through Day 15 for SAD and Day 29 for MAD. | Assess Incidence, severity, causality, and clinical outcome of serious adverse events (SAEs) graded per CTCAE Version 6.0 to characterize the safety and tolerability of HL40626S in Part 1 (SAD) and Part 2 (MAD). |
| Parts 1 (SAD) and 2 (MAD): Proportion of participants with clinically significant abnormal findings in physical examinations, vital signs, clinical laboratory tests, and 12-lead ECG assessments relative to baseline [Safety and Tolerability] | From signed informed consent through Day 15 for SAD and Day 29 for MAD. | Abnormal findings from physical examinations, vital sign measurements, laboratory analyses and 12-lead ECG tracings are compared against each participant's baseline values to support the overall safety and tolerability assessment of HL40626S in Part 1 (SAD) and Part 2 (MAD). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 (SAD): Maximum observed plasma concentration (Cmax) | Predose up to 5 days post single dose. | Calculate peak plasma HL40626S concentration following a single fasting oral administration |
| Part 1 (SAD): Time to maximum observed plasma concentration (Tmax) | Predose up to 5 days post single dose. | Record the time point corresponding to the observed Cmax after single fasting oral administration. |
| Part 1 (SAD): Area under the plasma concentration-time curve from time zero to last measurable concentration (AUClast) | Predose up to 5 days post single dose. | Calculate AUClast via plasma concentration data collected over the sampling period following single-dose administration. |
| Part 1 (SAD): Area under the plasma concentration-time curve extrapolated to infinite time (AUCinf) | Predose up to 5 days post single dose. | Assess the area under the plasma concentration-time curve extrapolated to infinite time (AUCinf) following single dose of HL40626S. |
| Part 1 (SAD): Terminal elimination rate constant (Kel) | Predose up to 5 days post single dose. | Calculate terminal elimination rate constant following single dose of HL40626S tablets. |
Countries
Australia
Contacts
CONTACTArockiaa P Aarthy Joseph, MBBS
Outcome results
None listed